Intratumoral Nerve Phased Development: A Promising Therapeutic Target

ABSTRACT The nervous system has emerged as a critical regulator of tumor biology, engaging in dynamic crosstalk with cancer cells. Although the protumorigenic role of innervation is well established, increasing attention is now directed toward reciprocal influences—how tumors actively shape and remodel local nerve networks within the tumor microenvironment, thereby contributing to the field of cancer neuroscience. Neuronal integration into tumors is a multistep process, beginning with the emergence of neurons in tumor‐adjacent regions and progressing through tumor‐driven neuritogenesis and axonogenesis, ultimately culminating in the formation of synapse‐like structures. Targeting these sequential stages of neuronal development, a strategy broadly termed denervation, offers novel therapeutic opportunities at the interface of oncology and neuroscience. Elucidating and disrupting this tumor–nerve axis may yield new strategies for cancer control and symptom management.